Pyridostigmine kinetics in healthy subjects and patients with myasthenia gravis

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Abstract
Comparative pyridostigmine kinetics in plasma measured in 10 healthy subjects given 4 mg i.v. and 60 mg oral pyridostigmine bromide. As determined from the AUC [area under the concentration curve] ratio, oral availability was 11.5%-18.9% (.hivin.X = 14.3%). Mean t1/2 [half life] of the plasma level decline after oral dosing was 200 min, twice as long as the terminal elimination t1/2 after i.v. infusion (97 min). Absorption may proceed at a slower rate than elimination. Comparison of intraindividual data revealed strict dependence of the AUC on the infused dose (2, 4 and 8 mg) in 1 subject and variability in AUC up to a factor of 2 when 2 subjects took oral pyridostigmine 3 times. Patients with myasthenia who were receiving continuous therapy with oral pyridostigmine had AUC values/unit dose corresponding to those in healthy subjects. Storage stability of pyridostigmine in plasma required acidification of samples and storage at -75.degree. C. When native plasma was kept at -20.degree. C, there was appreciable loss of pyridostigmine within 1-2 mo., the extent of which depended on the initial concentration.

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